基于序列特征的环状RNA识别

环状RNA是新发现的一类具有重要生物学功能的RNA。现有的环状RNA识别工具依赖高通量测序数据,因数据本身和识别方式的弊端而普遍存在准确性不足、不同方法间重复性低以及假阳性率/假阴性率高等缺点。为了解决该问题,我们搭建模型来实现不依赖于测序数据而根据序列的内在特征的环状RNA从头预测。本文选取了包括剪接位点上下游内含子的长度、A-to-I密度和Alu重复序列等100个与RNA成环相关的序列特征,建立了机器学习模型,并识别了人类基因组中的环状RNA,比较了两种机器学习方法随机森林法(RF)和支持向量机(SVM)的分类效果。结果表明,所选序列特征能有效地鉴别RNA能否成环,同时,不同序列特征对模型的分类预测能力的贡献也不同。相比于SVM方法,RF分类的效果更好。     

恶性疟原虫abstrakt同源基因的克隆及DEAD盒家族蛋白的序列分析

DEAD盒蛋白家族的ATP依赖性的RNA解旋酶类参与细胞内几乎所有的RNA代谢过程 ,在几乎所有生物的细胞生长发育过程中扮演着众多不可或缺的角色。在本实验中 ,通过PCR和探针杂交相结合的筛选方法 ,筛选恶性疟原虫 (Plasmodiumfalciparum)的基因组文库 ,克隆了FH1F———abstrakt同源基因的完整序列。通过搜索已经完成测序的恶性疟原虫基因组数据库 ,推测FH1F序列定位在第 5条染色体上。FH1F全长2 80 4bp,包含一个 1 1 6 1bp的完整阅读框 ,编码一个由 386个氨基酸组成的蛋白。对FH1F蛋白序列用BlastP进行搜索和分析以及用DNAStar与许多典型的DEAD盒蛋白序列进行比对分析 ,结果均提示FH1F蛋白应该是DEAD盒家族的一个Abstrakt蛋白。另一方面 ,用DNAStar对已知所有完整的DEAD盒蛋白进行详细的序列分析以及用Mega对这些序列进行系统发育研究的结果都显示 :DEAD盒家族的蛋白聚类成为若干不同的亚群 ;与DEAD盒蛋白的一般保守序列相比 ,Abstrakt,eIF 4A ,Vasa ,P6 8等不同亚群的DEAD盒蛋白在保守区具有各自不同的结构特征。本文对不同的DEAD盒蛋白的结构特征进行了总结并试图给出不同亚群分类上的结构标准 ,对Abstrakt蛋白在本应高度保守的位点上异常于其它DEAD盒蛋白的氨基酸残基的取代也进行了相关的初步分析     

Application of discrete Fourier inter-coefficient difference for assessing genetic sequence similarity

Digital signal processing (DSP) techniques for biological sequence analysis continue to grow in popularity due to the inherent digital nature of these sequences. DSP methods have demonstrated early success for detection of coding regions in a gene. Recently, these methods are being used to establish DNA gene similarity. We present the inter-coefficient difference (ICD) transformation, a novel extension of the discrete Fourier transformation, which can be applied to any DNA sequence. The ICD method is a mathematical, alignment-free DNA comparison method that generates a genetic signature for any DNA sequence that is used to generate relative measures of similarity among DNA sequences. We demonstrate our method on a set of insulin genes obtained from an evolutionarily wide range of species, and on a set of avian influenza viral sequences, which represents a set of highly similar sequences. We compare phylogenetic trees generated using our technique against trees generated using traditional alignment techniques for similarity and demonstrate that the ICD method produces a highly accurate tree without requiring an alignment prior to establishing sequence similarity.     

GPGPU加速生物序列比对研究进展

序列比对是生物信息学中最常用和最经典的研究手段。生物序列比对需要有强大计算能力的硬件支撑,而近年快速发展起来的GPGPU正好可堪此任。本文首先介绍GPGPU的发展过程,进而讲述GPGPU硬件设备与其编程环境,然后对GPGPU做科学计算时需要的数学库函数做一介绍,最后综述近年来国内外基于GPGPU的生物序列比对软件和相关研究工作,并总结和展望其辉煌前景。     

The Molecular Clock Runs at Different Rates Among Closely Related Members of a Gene Family

The serum albumin gene family is composed of four members that have arisen by a series of duplications from a common ancestor. From sequence differences between members of the gene family, we infer that a gene duplication some 580 Myr ago gave rise to the vitamin D–binding protein (DBP) gene and a second lineage, which reduplicated about 295 Myr ago to give the albumin (ALB) gene and a common precursor to α-fetoprotein (AFP) and α-albumin (ALF). This precursor itself duplicated about 250 Myr ago, giving rise to the youngest family members, AFP and ALF. It should be possible to correlate these dates with the phylogenetic distribution of members of the gene family among different species. All four genes are found in mammals, but AFP and ALF are not found in amphibia, which diverged from reptiles about 360 Myr ago, before the divergence of the AFP-ALF progenitor from albumin. Although individual family members display an approximate clock-like evolution, there are significant deviations—the rates of divergence for AFP differ by a factor of 7, the rates for ALB differ by a factor of 2.1. Since the progenitor of this gene family itself arose by triplication of a smaller gene, the rates of evolution of individual domains were also calculated and were shown to vary within and between family members. The great variation in the rates of the molecular clock raises questions concerning whether it can be used to infer evolutionary time from contemporary sequence differences. Received: 28 February 1995 / Accepted: 6 October 1997     

Isolation and analysis of a cDNA clone that encodes an alfalfa (Medicago sativa) aspartate aminotransferase

Summary Nitrate reductase (NR) assays revealed a bi-specific NAD(P)H-NR (EC 1.6.6.2.) to be the only nitrate-reducing enzyme in leaves of hydroponically grown birches. To obtain the primary structure of the NAD(P)H-NR, leaf poly(A)⁺ mRNA was used to construct a cDNA library in the lambda gt11 phage. Recombinant clones were screened with heterologous gene probes encoding NADH-NR from tobacco and squash. A 3.0 kb cDNA was isolated which hybridized to a 3.2 kb mRNA whose level was significantly higher in plants grown on nitrate than in those grown on ammonia. The nucleotide sequence of the cDNA comprises a reading frame encoding a protein of 898 amino acids which reveals 67%–77% identity with NADH-nitrate reductase sequences from higher plants. To identify conserved and variable regions of the multicentre electron-transfer protein a graphical evaluation of identities found in NR sequence alignments was carried out. Thirteen well-conserved sections exceeding a size of 10 amino acids were found in higher plant nitrate reductases. Sequence comparisons with related redox proteins indicate that about half of the conserved NR regions are involved in cofactor binding. The most striking difference in the birch NAD(P)H-NR sequence in comparison to NADH-NR sequences was found at the putative pyridine nucleotide binding site. Southern analysis indicates that the bi-specific NR is encoded by a single copy gene in birch. These sequence data appeared in the EMBL/GenBank/DDBJ nucleotide sequence data bases under the accession number X54097     

Algorithm independent properties of RNA secondary structure predictions

Algorithms predicting RNA secondary structures based on different folding criteria – minimum free energies (mfe), kinetic folding (kin), maximum matching (mm) – and different parameter sets are studied systematically. Two base pairing alphabets were used: the binary GC and the natural four-letter AUGC alphabet. Computed structures and free energies depend strongly on both the algorithm and the parameter set. Statistical properties, such as mean number of base pairs, mean numbers of stacks, mean loop sizes, etc., are much less sensitive to the choice of parameter set and even of algorithm. Some features of RNA secondary structures, such as structure correlation functions, shape space covering and neutral networks, seem to depend only on the base pairing logic (GC or AUGC alphabet). Received: 16 May 1996 / Accepted: 10 July 1996     

Sequence instability in the long terminal repeats of avian spleen necrosis virus and reticuloendotheliosis virus

Summary Sequence divergence between the 3 long terminal repeats (LTR) of avian reticuloendotheliosis virus (REV), deletion variant proviral clone 2-20-4, and spleen necrosis virus (SNV)—proviral clones 14-44, 60, and 70—was found to involve two classes of base substitutions: low-frequency interspersed and high-frequency clustered substitutions. Clones 2-20-4 and 14-44 have diverged 4.4% owing to low-frequency substitutions. In contrast, two high-frequency substitution segments have diverged by 30% and 29%, respectively. Clustered substitutions appear to be located either within or next to tandem repeats, suggesting their introduction concomitant with sequence deletions and duplications commonly associated with such repeats. A new 19-bp tandem repeat is found in clone 2-20-4. Its sequence could have evolved from the 26-bp repeats found in the SNV clones.     

SARS病毒与其他冠状病毒的基因组比较

本文利用生物信息学方法比较SARS病毒和其他冠状病毒基因组.通过数据库搜索,找出与SARS病毒基因组相似的核酸或蛋白质序列,并对相似序列进行比对,分析它们的共性和差异.结果表明,SARS病毒在基因组的组织上及结构蛋白质方面与现有冠状病毒有比较大的相似性,SARS病毒基因组与冠状病毒基因组相关.但是,SARS病毒基因组还存在一些特异性序列,ORF1a和S蛋白(特别是S1)的变化以及SARS-CoV特异性的非结构蛋白可能是SARS发病机理与传染特性区别于其他冠状病毒的分子基础.在全基因组水平上进行核酸单词出现频率分析,结果表明,SARS病毒远离已知的其他冠状病毒,单独成为一类.